At the present time, there are drugs available which affect the metabolism of kidney cells, influence renal blood flow, alter water and electrolyte excretion and other functions of the kidney. A serious drawback of some of these drugs is that they exert their pharmacological activity on parts of the system other than the kidney and thereby cause toxicities and undesirable systemic side effects such as acceleration in heart rate, and elevation of blood pressure.
Such problematic systemic effects are often reported in the pharmacology of dopamine (Formula I) and its metabolic precursor L-DOPA (Formula II). ##STR1##
L-DOPA is a compound that is metabolized in the body of mammals, including man, by aromatic amino acid decarboxylase to dopamine (Christenson et al., Arch. Biochem. Biophys. 141: 356, 1970). Dopamine is a naturally occuring catecholamine considered to be a precursor of norepinephrine. Dopamine plays an important role as a neurotransmitter in the central nervous system and as an inhibitory transmitter in autonomic ganglia. The ability of dopamine to interact with .alpha. and .beta. receptors in the body often leads to undesirable side effects such as changes in systemic hemodynamics and increases in cardiac output and gangrene. U.S. Pat. No. 3,903,147 and U.S Pat. No. 3,947,590 disclose that this problem is encountered when dopamine is used to increase renal blood flow. U.S. Pat. No. 3,769,424 discloses similar systemic problems when L-DOPA is used as an anti-Parkinson drug to treat disturbances in the brain.
U.S. Pat. No. 3,903,147 and U.S. Pat. No. 3,947,590 disclose the use of a dopamine derivative, .gamma.-glutamyl-dopamine to increase renal blood flow in the kidney without desirable systemic hemodynamic changes. Although these patents disclose the fact that .gamma.-glutamyl-dopamine is a specific renal vasodilator it does not disclose the mechanism by which that effect was achieved.
According to the method of this invention, the .gamma.-glutamyl derivative of DOPA ##STR2## is used as a specific renal vasodilator.